1. Field of the Invention
The present invention relates to a controlled-releasing medicament-containing preparation for intra-oral use, and is more especially concerned with such a preparation (and the process of using it) in the form of a very thin extruded thermoplastic film (which can be in single layer or laminated multi-layer form) having at least one bioadhesive layer containing .[.40-95.]..Iadd.20-93.Iaddend.% of a thermoplastic cellulose ether and 5-60% of a homopolymer of ethylene oxide which can adhere to the mucosa of the oral cavity. The extruded film drug delivery system of the present invention, which has incorporated therein the medicament to be dispensed, is so thin and flexible when wet as to be unobtrusive to the patient after it has been properly positioned and placed in the mouth.
2. Description of the Prior Art
Several systems have previously been described which pertain to the delivery of drugs into the oral cavity. These include:
1. Treatment of periodontal disease with tetracycline, chlorhexidine or metronidazole loaded into hollow cellulose acetate fibers. These fibers are packed in the periodontal pockets and provide controlled release of the drug to the infected area. PA0 2. Cast films containing ethyl cellulose/propylene glycol with chlorhexidine or metronidazole for treatment of periodontal disease. PA0 3. An orthodontic appliance with a hydroxyethyl methacrylate/methyl methacrylate copolymer (HEMA/MMA) matrix. Sodium fluoride is incorporated into the HEMA/MMA matrix to provide sustained fluoride release and enhanced anticaries activity. HEMA/MMA with fluoride may also be attached to the tooth in the form of a wafer-like tablet. PA0 4. Silicone/ethyl cellulose/polyethylene glycol films containing sodium fluoride are applied as coatings on orthodontic bands or in chewing gum. Controlled release of fluoride and anticaries activity is claimed. The above systems are discussed in the "The Compendium of Continuing Education" Vol VI, No. 1, January 1985 p. 27-36 review article "Controlled Drug Delivery: A New Means of Treatment of Dental Disease", by J. Max Goodson, D.D.S., Ph.D. of the Forsyth Dental Center. Other systems, described in GB patent application No. 2,042,888 and U.S. Pat. Nos. 4,292,299/4,226,848 (Teijin Ltd., Japan), use combinations of cellulosic and polyacrylate polymers. The preferred materials are hydroxypropyl cellulose ("Klucel") and a copolymer of acrylic acid ("Carbopol") that is administered in the form of thin tablets (discs), granules or powder. Other polymers that might be added are vinyl copolymers, polysaccharides, gelatin and collagen. U.S. Pat. No. 4,517,173 (Nippon Soda Co. Ltd, Japan) uses various celluloses in a multi-layered non-extruded cast film preparation. PA0 Anesthetics/Analgesics-benzocaine, dyclonine HCl, phenol, aspirin, phenacetin, acetaminophen, potassium nitrate, etc. PA0 Anticaries Agents-sodium fluoride, sodium monofluorophosphate, stannous fluoride, etc. PA0 Anti-inflammatories-hydrocortisone acetate, triamcinolone acetonide, dipotassium, glycyrrhizinate, etc. PA0 Antihistamines-chlorpheniramine maleate, ephedrine HCL, diphenhydramine HCL, etc. PA0 Antibiotics-i.e., tetracycline, doxycycline hyclate, meclocycline, minocycline, etc.
Examples of prior art products currently on the market include ointments such as ORABASE* with Benzocaine (Squibb), Kenalog* (Triamcinolone Acetonide) in ORABASE* (Squibb) and Mycostatin* (Nystatin) ointment (Squibb).
The prior art products and delivery systems described above are useful but have the following disadvantages:
Tablets, appliances, hollow fibers are "bulky" in the mouth, are difficult to keep in place and inconvenient to apply. PA1 Ethyl cellulose and/or silicone films do not adhere to mucosal tissue. PA1 Ointments (i.e., ORABASE*) have an unpleasant feel and do not last very long. PA1 Except for ORABASE*, all the foregoing systems require professional application to the tooth or periodontal pockets.
The bioadhesive film of the present invention alleviates many of the above problems. It may be applied easily by the consumer. It has very little or no mouthfeel, it has good adhesion to the mucosal tissues, and provides controlled release of the medicament.